Department of Ultrasound, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
Int J Oncol. 2013 Jul;43(1):151-8. doi: 10.3892/ijo.2013.1921. Epub 2013 Apr 25.
Gene therapy is a potentially viable approach for treating hormone-refractory prostate cancer (HRPC), it requires efficient delivery systems and a target gene. Inducing carcinoma cell apoptosis by inhibition of heat shock protein 70 (HSP70) overexpression has been emerging as an attractive strategy for cancer therapy. In our study, the high tumor-specificity of human telomerase reverse transcriptase (HTERT) expression prompted the use of an HTERT/cytomegalovirus (CMV) chimeric promoter to drive HSP70-ShRNA expression to induce HRPC 22RV1 cell apoptosis. At the same time, sonoporation induced by ultrasound-targeted microbubble destruction (UTMD) was utilized for delivery of plasmid loaded with HTERT/CMV promoter. Our results indicated the combination of sonoporation, low-dose liposomes and HTERT/CMV chimeric promoter as a delivery system has the potential to promote efficient gene transfer with lower cytotoxicity.
基因治疗是治疗激素难治性前列腺癌(HRPC)的一种有潜力的方法,它需要高效的传递系统和靶基因。通过抑制热休克蛋白 70(HSP70)的过表达来诱导癌细胞凋亡已成为癌症治疗的一种有吸引力的策略。在我们的研究中,人端粒酶逆转录酶(hTERT)表达的高肿瘤特异性促使我们使用 hTERT/巨细胞病毒(CMV)嵌合启动子来驱动 HSP70-ShRNA 的表达,从而诱导 HRPC 22RV1 细胞凋亡。同时,利用超声靶向微泡破坏(UTMD)诱导的声孔作用来递送带有 hTERT/CMV 启动子的质粒。我们的结果表明,声孔作用、低剂量脂质体和 hTERT/CMV 嵌合启动子的组合作为一种传递系统具有促进高效基因转移和降低细胞毒性的潜力。